青少年成人脊髓性肌萎缩症临床诊疗指南

中国研究型医院学会罕见病分会; 中国罕见病联盟; 北京罕见病诊疗与保障学会; 青少年成人脊髓性肌萎缩症临床诊疗指南中国专家组

doi:10.12376/j.issn.2097-0501.2023.01.010

文章导航 > 罕见病研究 > 2023 > 2(1): 70-84

中国研究型医院学会罕见病分会, 中国罕见病联盟, 北京罕见病诊疗与保障学会, 青少年成人脊髓性肌萎缩症临床诊疗指南中国专家组. 青少年成人脊髓性肌萎缩症临床诊疗指南[J]. 罕见病研究, 2023, 2(1): 70-84. doi: 10.12376/j.issn.2097-0501.2023.01.010

引用本文:

Rare Disease Society of Chinese Research Hospital Association, China Alliance for Rare Diseases, Beijing Society of Rare Disease Clinical Care and Accessibility, China Expert Group for Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy. Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy[J]. Journal of Rare Diseases, 2023, 2(1): 70-84. doi: 10.12376/j.issn.2097-0501.2023.01.010

Citation:

Rare Disease Society of Chinese Research Hospital Association, China Alliance for Rare Diseases, Beijing Society of Rare Disease Clinical Care and Accessibility, China Expert Group for Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy. Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy[J]. Journal of Rare Diseases, 2023, 2(1): 70-84. doi: 10.12376/j.issn.2097-0501.2023.01.010

引用本文:

Citation:

Rare Disease Society of Chinese Research Hospital Association, China Alliance for Rare Diseases, Beijing Society of Rare Disease Clinical Care and Accessibility, China Expert Group for Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy. Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy[J]. Journal of Rare Diseases, 2023, 2(1): 70-84. doi: 10.12376/j.issn.2097-0501.2023.01.010

青少年成人脊髓性肌萎缩症临床诊疗指南

doi: 10.12376/j.issn.2097-0501.2023.01.010

1.
中国医学科学院北京协和医院神经科，北京 100730
2.
中国医学科学院北京协和医院疑难重症与罕见病国家重点实验室，北京 100730

基金项目: 中央高水平医院临床科研业务费(2022-PUMCH-D-002)；本研究为中国医学科学院罕见病研究中心支持项目

通信作者：戴毅^1，2，E-mail：pumchdy@pumch.cn
崔丽英^1，2，E-mail：pumchcuily@sina.com

详细信息

中图分类号: R746.4
计量
- 文章访问数: 318
- HTML全文浏览量: 73
- PDF下载量: 199
- 被引次数: 0
出版历程
- 收稿日期: 2023-01-04
- 录用日期: 2023-01-18

Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy

1.
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funding: National High Level Hospital Clinical Research Funding (2022-PUMCH-D-002); This Work was Supported by Center for Rare Diseases Research, Chinese Academy of Medical Sciences, Beijing, China

摘要

摘要: 近年来，脊髓性肌萎缩症(SMA)在多学科综合管理、疾病修正治疗药物等方面取得长足进步，明显提升了患者生存期及生活质量。然而，对于年龄较大的青少年与成人患者尚缺乏系统性临床诊疗指南规范指导临床工作。基于循证医学原则，来自全国多家SMA诊疗中心的多学科专家经过充分讨论，达成一致意见，为SMA临床规范化诊疗提供重要依据。
- 脊髓性肌萎缩症 /
- 诊断 /
- 多学科管理 /
- 疾病修正治疗
Abstract: In recent years, spinal muscular atrophy (SMA) has made progress in multidisciplinary treatment and disease-modifying therapeutic drugs, so that the progress has significantly improved the survival and quality of life of the patients. However, no clinical practice guideline has developed for the management of SMA in adults and adolescents patients. Experts of multidisciplinary from a number of tertiary medical centers in China who specialize in the diagnosis and treatment of SMA have come to an agreement based on evidence-based medicine. This guideline serves as instrumental reference for the standardized care of the Chinese SMA patients.
- spinal muscular atrophy /
- diagnosis /
- multidisciplinary treatment /
- disease modifying therapy
注释:

作者贡献：通信作者(戴毅、崔丽英)负责整个指南的筹划、专家团队组建，并负责整体推进指南的制定。12个专科部分的主要执笔人在各部分后标出。所有专家都参与了相应部分指南的讨论、提出大量修改意见，对指南进行了完善。最终实现所有专家均认可的终稿，予以投稿发表。

利益冲突：参与指南制定的全部专家均声明无利益冲突。

HTML全文

表 1 推荐强度与证据级别标准

Table 1. Recommended intensity and level of evidence criteria

项目	分级	具体标准
推荐强度(分四级，Ⅰ级最强，Ⅳ级最弱)	Ⅰ级	基于A级证据或专家高度一致的共识
	Ⅱ级	基于B级证据和专家共识
	Ⅲ级	基于C级证据和专家共识
	Ⅳ级	基于D级证据和专家共识
治疗措施的证据等级(分四级，A级最高，D级最低)	A级	基于多个随机对照试验的荟萃分析或系统评价；多个随机对照试验或1个样本量足够的机对照试验(高质量)
	B级	基于至少1个较高质量的随机对照试验
	C级	基于未随机分组但设计良好的对照试验，或设计良好的队列研究或病例对照研究
	D级	基于无同期对照的系列病例分析或专家意见
诊断措施的证据等级(分四级，A级最高，D级最低)	A级	基于多个或1个样本量足够、采用了参考(金)标准、盲法评价的前瞻性队列研究(高质量)
	B级	基于至少1个前瞻性队列研究或设计良好的回顾性病例对照研究，采用了金标准和盲法评价(较高质量)
	C级	基于回顾性、非盲法评价的对照研究
	D级	基于无同期对照的系列病例分析或专家意见

下载: 导出CSV

表 2 脊髓性肌萎缩症(SMA)国际分型

Table 2. International classification of spinal muscular atrophy(SMA)

分型	OMIM	起病年龄	运动里程碑	临床表现	亚型	自然病程	SMN2拷贝数
0型	-	出生前	无	仅有眼外肌活动，无任何活动。先天性关节挛缩，可合并先天性心脏病。出生后即需呼吸支持。	-	数日至1个月死亡	1
1型	253300	＜6月龄	不能独坐	软婴，肢体无力、活动少。头面部肌肉力弱。钟型胸。反复出现呼吸道感染及呼吸衰竭。	1a：2周内发病，无头控能力1b：1~3月发病，无正常头控能力1c：3~6月发病，可获得头控能力	1a：半岁内死亡1b：2岁内死亡1c：中位生存期17岁	1a主要为11b主要为21c主要为3
2型	253550	6~18月龄	独坐，不能独站独走	运动发育明显落后。上肢肌力随年龄增长而下降，后期出现关节挛缩、脊柱侧凸、胸廓变形。	2a: 独坐能力短期获得，后期丧失2b: 独坐能力长期保持	超过70%存活至25岁以上	主要3
3型	253400	＞18月龄	可独站独走	儿童期逐渐出现下肢近端起始，向上下发展的肢体无力萎缩，丧失行走能力后渐出现脊柱侧凸、关节挛缩、呼吸功能不全。	3a: 18~36月发病3b: ＞36月发病，进展更慢	存活至成年期，寿命轻度下降	3或4
4型	271150	成人期	获得跑跳等运动能力	成人起病，下肢起始的四肢近端力弱，病情缓慢进展。	-	寿命一般不受影响	≥4

下载: 导出CSV

表 3 SMA国际分型(修订版)

Table 3. International classification of SMA (revised version)

分型	OMIM	起病年龄	运动里程碑	临床表现	亚型	自然病程	SMN2拷贝数
0型	-	出生前	无	仅有眼外肌活动，无任何活动。先天性关节挛缩，可合并先天性心脏病。出生后即需呼吸支持。	-	数日至1个月死亡	1
1型	253300	＜6月龄	不能独坐	软婴，肢体无力、活动少。头面部肌肉力弱。钟型胸。反复出现呼吸道感染及呼吸衰竭。	1a：2周内发病，无头控能力1b：1~3月发病，无正常头控能力1c：3~6月发病，可获得头控能力	1a：半岁内死亡1b：2岁内死亡1c：中位生存期17岁	1a主要为11b主要为21c主要为3
2型	253550	6~18月龄	独坐，不能独站独走	运动发育明显落后。上肢肌力随年龄增长而下降，后期出现关节挛缩、脊柱侧凸、胸廓变形。	2a：独坐能力短期获得，后期丧失2b：独坐能力长期保持	超过70%存活至25岁以上	主要为3
3型	253400	＞18月龄	可独站独走	儿童期逐渐出现下肢近端起始，向上下发展的肢体无力萎缩，丧失行走能力后渐出现脊柱侧凸、关节挛缩、呼吸功能不全。	3a：18~36月发病，10岁前丧失行走能力3b：＞3岁发病，青春期前后病情明显加重，丧失行走能力。3c：＞12岁发病，行走能力长期保持，终生无明显脊柱侧弯。	存活至成年期，生存期可能轻度缩短	3或4
4型	271150	＞21岁	跑跳等所有运动能力	临床症状轻，运动及生活自理能力较正常人群无明显差异。	-	生存期一般不受影响	4或5

下载: 导出CSV

表 4 青少年成人SMA患者首次住院推荐评估项目

Table 4. Recommended assessment items for first hospitalization in adolescent adult SMA patients

类型	具体项目
生命体征与一般指标	体重体温心率收缩压和舒张压呼吸频率
血液检验	1.血常规、尿常规+沉渣、便常规+潜血、8 h尿微量白蛋白 2.肝肾脂全、胱抑素C、肌酸激酶+肌酸激酶同工酶+肌红蛋白 3.凝血、感染4项4.血气分析 5.血β-人绒毛膜促性腺激素
检查	1.X线或CT骨密度 2.脊柱CT+三维重建 3.全脊柱拼接相(拟行脊柱侧凸手术患者加做) 4.肺功能(通气+容量+弥散) 5.腰椎MRI 6.颈椎MRI(部分可能选择颈椎入路患者加做) 7.头MRI(除外其他可能合并疾病，监测药物治疗可能副作用) 8.超声心动图 9.心电图 10.肝胆胰脾双肾B超 11.胸部CT 12.电生理评估：复合肌肉动作电位(CMAP)、运动单位数量指数(MUNIX) 等
量表及功能评估	详见康复评估部分(本刊后续报道)
脑脊液检测	蛛网膜下腔穿刺成功，确认脑脊液持续顺畅流出，测定脑脊液压力及滴速，留取脑脊液样本完善脑脊液常规、生化、细胞学、寡克隆区带检测，剩余样本分装后-80 ℃冰箱保存

下载: 导出CSV

参考文献(37)

[1]	Zhang J, Wang Y, Ma D, et al. Carrier screening and prenatal diagnosis for spinal muscular atrophy in 13, 069 Chinese pregnant women[J]. J Mol Diagn, 2020, 22(6): 817-822. doi: 10.1016/j.jmoldx.2020.03.001
[2]	Lin Y, Lin C, Yin X, et al. Newborn screening for spinal muscular atrophy in China using DNA mass pectrometry[J]. Front Genet, 2019, 10: 1255. doi: 10.3389/fgene.2019.01255
[3]	Werdnig G. Die frühinfantile progressive spinale Amyo-trophie[M]. Archiv fur Psychiatrie und Nervenkran-kheiten, Berlin, 1894, 26: 707-744.
[4]	Brzustowicz LM, Lehner T, Castilla LH, et al. Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3[J]. Nature, 1990, 344: 540-541. doi: 10.1038/344540a0
[5]	Melki J, Abdelhak S, Sheth P, et al. Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q[J]. Nature, 1990, 344: 767-768. doi: 10.1038/344767a0
[6]	Lefebvre S, Burglen L, Reboullet S, et al. Identification and characterisation of a spinal muscular atrophy-determining gene[J]. Cell, 1995, 80: 155-165. doi: 10.1016/0092-8674(95)90460-3
[7]	北京医学会罕见病分会, 北京医学会医学遗传学分会, 北京医学会神经内科分会, 等. 脊髓性肌萎缩症多学科管理专家共识[J]. 中华医学杂志, 2019, 99(19): 1460-1467. doi: 10.3760/cma.j.issn.0376-2491.2019.19.006
[8]	北京医学会医学遗传学分会, 北京罕见病诊疗与保障学会. 脊髓性肌萎缩症遗传学诊断专家共识[J]. 中华医学杂志, 2020, 100(40): 3130-3140. doi: 10.3760/cma.j.cn112137-20200803-02267
[9]	中华医学会医学遗传学分会遗传病临床实践指南撰写组. 脊髓性肌萎缩症的临床实践指南[J]. 中华医学遗传学杂志, 2020, 37(3): 263-268. doi: 10.3760/cma.j.issn.1003-9406.2020.03.007
[10]	脊髓性肌萎缩症胚胎着床前遗传学检测专家共识编写组. 脊髓性肌萎缩症的胚胎着床前遗传学检测专家共识[J]. 中华医学遗传学杂志, 2022, 39(2): 129-134. doi: 10.3760/cma.j.cn511374-20210118-00048
[11]	Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy[J]. J Child Neurol, 2007, 22(8): 1027-1049. doi: 10.1177/0883073807305788
[12]	Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care[J]. Neuromuscul Disord, 2018, 28(2): 103-115. doi: 10.1016/j.nmd.2017.11.005
[13]	Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy: Part 2: pulmonary and acute care; medications, supplements and immuniza-tions; other organ systems; and ethics[J]. Neuromuscul Disord, 2018, 28(3): 197-207. doi: 10.1016/j.nmd.2017.11.004
[14]	Munsat TL. Workshop report: international SMA collabora-tion[J]. Neuromuscul Disord, 1991, 1: 81-83. doi: 10.1016/0960-8966(91)90052-T
[15]	Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era[J]. Muscle Nerve, 2015, 51(2): 157-167. doi: 10.1002/mus.24497
[16]	Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy[J]. N Engl J Med, 2018, 378(7): 625-635. doi: 10.1056/NEJMoa1710504
[17]	Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy[J]. N Engl J Med, 2017, 377(18): 1723-1732. doi: 10.1056/NEJMoa1702752
[18]	Hagenacker T, Wurster CD, Günther R, et al. Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study[J]. Lancet Neurol, 2020, 19(4): 317-325. doi: 10.1016/S1474-4422(20)30037-5
[19]	Gavriilaki M, Moschou M, Papaliagkas V, et al. Nusiner-sen in adults with 5q spinal muscular atrophy: a systematic review and meta-analysis[J]. Neurotherapeutics, 2022, 19(2): 464-475. doi: 10.1007/s13311-022-01200-3
[20]	Mercuri E, Deconinck N, Mazzone ES, et al. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial[J]. Lancet Neurol, 2022, 21(1): 42-52. doi: 10.1016/S1474-4422(21)00367-7
[21]	Prior TW. Spinal muscular atrophy: a time for screening[J]. Curr Opin Pediatr, 2010, 22(6): 696-702. doi: 10.1097/MOP.0b013e32833f3046
[22]	Committee on Genetics. Committee opinion No. 691: carrier screening for genetic conditions[J]. Obstet Gynecol, 2017, 129(3): e41-e55. doi: 10.1097/AOG.0000000000001952
[23]	Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges[J]. Lancet Neurol, 2012, 11(5): 443-452. doi: 10.1016/S1474-4422(12)70061-3
[24]	Marasco LE, Dujardin G, Sousa-Luís R, et al. Counteracting chromatin effects of a splicing-correcting antisense oligonucleotide improves its therapeutic efficacy in spinal muscular atrophy[J]. Cell, 2022, 185(12): 2057-2070, e15. doi: 10.1016/j.cell.2022.04.031
[25]	Darras BT, Chiriboga CA, Iannaccone ST, et al. Nusiner-sen in later-onset spinal muscular atrophy: long-term results from the phase 1/2 studies[J]. Neurology, 2019, 92(21): e2492-e2506. doi: 10.1212/WNL.0000000000007527
[26]	姜源, 夏雨, 李海冰, 等. 脊髓性肌萎缩症患者肺功能分析[J]. 中华实用儿科临床杂志, 2022, 37(12): 914-919. doi: 10.3760/cma.j.cn101070-20210610-00662
[27]	Ortolan P, Zanato R, Coran A, et al. Role of radiologic imaging in genetic and acquired neuromuscular disorders[J]. Eur J Transl Myol, 2015, 25(2): 5014.
[28]	Chan WP, Liu GC. MR imaging of primary skeletal muscle diseases in children[J]. AJR Am J Roentgenol, 2002, 179(4): 989-997. doi: 10.2214/ajr.179.4.1790989
[29]	Mercuri E, Cini C, Counsell S, et al. Muscle MRI findings in a three-generation family affected by Bethlem myopathy[J]. Eur J Paediatr Neurol, 2002, 6(6): 309-314. doi: 10.1053/ejpn.2002.0618
[30]	Masson R, Brusa C, Scoto M, et al. Brain, cognition, and language development in spinal muscular atrophy type 1: a scoping review[J]. Dev Med Child Neurol, 2021, 63(5): 527-536. doi: 10.1111/dmcn.14798
[31]	Querin G, El Mendili MM, Lenglet T, et al. The spinal and cerebral profile of adult spinal-muscular atrophy: a multimodal imaging study[J]. Neuroimage Clin, 2019, 21: 101618. doi: 10.1016/j.nicl.2018.101618
[32]	de Borba FC, Querin G, França MC Jr, et al. Cerebellar degeneration in adult spinal muscular atrophy patients[J]. J Neurol, 2020, 267(9): 2625-2631. doi: 10.1007/s00415-020-09875-4
[33]	Stam M, Haakma W, Kuster L, et al. Magnetic resonance imaging of the cervical spinal cord in spinal muscular atrophy[J]. Neuroimage Clin, 2019, 24: 102002. doi: 10.1016/j.nicl.2019.102002
[34]	Laufersweiler-Plass C, Rudnik-Schneborn S, Zerres K, et al. Behavioural problems in children and adolescents with spinal muscular atrophy and their siblings[J]. Dev Med Child Neurol, 2003, 45(1): 44-49.
[35]	Stefania LF, Cristina F, Maria S, et al. Intrathecal administration of Nusinersen in type 1 SMA: successful psychological program in a single Italian center[J]. Neurol Sci, 2018, 39(11): 1961-1964. doi: 10.1007/s10072-018-3506-z
[36]	Ropars J, Peudenier S, Genot A, et al. Multidisciplinary approach and psychosocial management of spinal muscular atrophy(SMA)[J]. Arch de Pediatr, 2020, 27(7S): 7S45-7S49.
[37]	Fischer MJ, Asselman FL, Kruitwagen-Van Reenen ET, et al. Psychological well-being in adults with spinal muscular atrophy: the contribution of participation and psychological needs[J]. Disabil Rehabil, 2020, 42(16): 2262-2270. doi: 10.1080/09638288.2018.1555864